Measurement of cerebral glucose metabolism (CMR-Glu) with 14C-deoxyglucose (DG) and 10F-fluorodeoxyglucose (FDG) has proven to be a valuable technique for studying both normal cerebral function and a variety of neurological diseases. However, this method is not quantitatively accurate under conditions of ischemia or hypoglycemia due to changes in the value of the isotope correction factor (lumped constant). The use of 11C-glucose labeled specifically at the 1-carbon position (1-22C-glucose) has several advantages: First, no correction factor is required. Second, almost all of the radioactive label is trapped as metabolites of intermediary metabolism within the first 5-10 minutes after injection providing adequate time for data collection. Development of a method to measure CMR-Glu with 1-22C glucose and positron emission tomography (PET) is critical for studies of blood brain glucose transport and cerebral glucose metabolism under conditions of cerebral ischemia and hypoglycemia. The specific hypothesis to be tested is: PET employing 1-22C-glucose can be use to measure cerebral glucose metabolism (CMR-Glu) accurately under a wide variety of physiological and pathological conditions, including cerebral ischemia and hypoglycemia. The specific aim of this project is to compare paired, simultaneous determinations of CMR-Glu in non-human primates by PET with 1-22C-glucose and by direct measurement of arterial-jugular venous (A- V) glucose differences assayed by mass spectrometry under conditions of cerebral ischemia, hypoglycemia, and hypoxemia as well as pharmacologically induced reductions and increased oxidative glycolysis. The accuracy of the PET method using two different models (four compartment and distributed parameter) under these various conditions will be determined. Under those conditions for which one particular model may provide a consistently accurate measurement of CMR-Glu, the estimated rate constants will be analyzed to determine what changes in forward and reverse glucose transport and phosphorylation have taken place. This analysis will provide insight into compensatory mechanisms used by the brain to maintain glucose metabolism under conditions of reduced supply or increased demand.